A crystallogenesis study of human transthyretin using the counter-diffusion method is described as an alternative to conventional convective vapour diffusion and batch approaches for protein crystallization. The X-ray diffraction results show systematic trends that exhibit unique patterns of crystallization and high crystal quality as well as a remarkable degree of coherence within extended crystal rods that wholly fill the capillaries used. Preliminary neutron diffraction data have been recorded from a number of these samples, validating the feasibility of this methodology for neutron crystallography.

Africa is the only habitable continent that is not yet host to a light source - an important tool across disciplines. Scientists from the Executive Committee of the African Light Source Foundation discuss work towards building an advanced light source in Africa, and what remains to be done.

An advanced light source (AdLS) presents itself as the most important scientific investment that Africa could construct at this point in its history. There is an urgent imperative to develop all the world’s socioeconomic prowess more equitably across its diversity. There needs to be a more universal and regionally balanced participation in the global economy. This would reflect in science becoming a truly global enterprise. This is rather fundamental, as innovation is the most important factor that drives economic development (Romer 1986). The crystal ball indicates that Africa will soon be home to the bulk of the world’s youth (United Nations, Department of Economic and Social Affairs, Population Division 2017). These young people will need to be engaged in the economy. Africa currently has a population of 1.2 billion, with 169 scientists per million people (UNESCO 2015a). This is a factor of 20 times less than the average of Europe. Africa therefore needs at least one million new scientists to drive its economic development through innovation. The vision of achieving sustainable and equitable development drives the logic of investment in science, technology, and innovation. All seventeen of the sustainable development goals of UNESCO must be progressed (UNESCO 2015b). The new large-scale scientific infrastructure must be both multi- and inter-disciplinary. The obvious candidate is the AdLS (LAAAMP 2018). Many have asked whether Africa is ready for such a technologically sophisticated large-scale scientific infrastructure. The answer is YES. Africa is long overdue for the acquisition of such an transformative instrument. Africa simply cannot afford to lag behind the rest of the world as now the only habitable continent without an AdLS. Some regions beyond Africa already have several generations of emerging career scientists trained to use this kind of premier tool for scientific enquiry. These second and later generations of scientists are now often active in industry, creating awareness and knowledge of the AdLS analytical and characterization prowess within the commercial world. With this impetus and also the outreach actions of AdLSs, many AdLSs worldwide now have dedicated industrial liaison or business development offices with the mission to engage with industry for exploitation of light source facilities and intellectual property). AdLSs have started to make the leap from academia to industry. They have progressed now to become a premier tool driving and supporting industrial innovation (biotechnology, nanotechnology, energy technology, and many more) through the advanced characterization of materials and living matter, going far beyond the capabilities of conventional X-ray sources. Several facilities, such as the APS (USA), SPring8 (Japan), and SLS (Switzerland) have beamlines wholly or partially owned by industry, and most light sources run significant commercial programmes with industry for proprietary access to the X-ray beamlines. Complementing this, it is important to note that engagement with industry is also significant through the public access programs where industry, usually in collaboration with academic teams, works on applied R&D with publishable results. This is an important engagement mechanism, supporting innovation via precompetitive research, and it is estimated that some 20–40% of public programs have industry relevance or engagement as part of the work being carried out. Of course, we can have African suitcase scientists, who travel abroad when they need to use international research facilities, such as AdLSs. But then, ultimately, we lose many of the elite emerging African scientists to the African science diaspora. Africa misses out on the mega-science techno-industrial research and manufacturing parks that emerge around significant local research infrastructural capacity. An AdLS is not only just about good science but also about retaining innovators and seeding local competitive industry. Indeed though, an AdLS has stringent requirements on political stability, reliable electrical energy, travel connections, and Internet bandwidth. Indeed, it also requires an established user base of active scientists and also a strong local technological capacity (see Table ​Table1).1). We have not said, indeed, that it requires financial capacity, since this aspect is simply about prioritization. An AdLS costs approximately half to one billion euros to construct, and a similar amount to operate, maintain, and upgrade every decade thereafter. Therefore, it is similar in cost to a football stadium, or a percentage of a large municipal railway system, or a large-scale power station. Thus, an AdLS is eminently affordable by the governments of Africa pooling their financial resources. Africa must just understand its contribution to transformation of continental socio-economics. Table 1 Requirements to host a synchrotron

Seed extracts from Moringa oleifera are of wide interest for use in water purification where they can play an important role in flocculation; they also have potential as anti-microbial agents. Previous work has focused on the crude protein extract. Here we describe the detailed biophysical characterization of individual proteins from these seeds. The results provide new insights relating to the active compounds involved. One fraction, designated Mo-CBP3, has been characterized at a molecular level using a range of biochemical and biophysical techniques including liquid chromatography, X-ray diffraction, mass spectrometry, and neutron reflection. The interfacial behavior is of particular interest in considering water purification applications and interactions with both charged (e.g. silica) and uncharged (alumina) surfaces were studied. The reflection studies show that, in marked contrast to the crude extract, only a single layer of the purified Mo-CBP3 binds to a silica interface and that there is no binding to an alumina interface. These observations are consistent with the crystallographic structure of Mo-CBP3-4, which is one of the main isoforms of the Mo-CBP3 fraction. The results are put in context of previous studies of the properties of the crude extract. This work shows possible routes to development of separation processes that would be based on the specific properties of individual proteins.

We describe the preparation of a novel self-assembling supramolecular nanotube system.

The application of IR spectroscopy to the characterization and quality control of samples used in neutron crystallography is described. While neutron crystallography is a growing field, the limited availability of neutron beamtime means that there may be a delay between crystallogenesis and data collection. Since essentially all neutron crystallographic work is carried out using D2O-based solvent buffers, a particular concern for these experiments is the possibility of H2O back-exchange across reservoir or capillary sealants. This may limit the quality of neutron scattering length density maps and of the associated analysis. Given the expense of central facility beamtime and the effort that goes into the production of suitably sized (usually perdeuterated) crystals, a systematic method of exploiting IR spectroscopy for the analysis of back-exchange phenomena in the reservoirs used for crystal growth is valuable. Examples are given in which the characterization of D2O/H2O back-exchange in transthyretin crystals is described.

In this report we show for the first time that neutron anomalous dispersion can be used in a practical manner to determine experimental phases of a protein crystal structure, providing a new tool for structural biologists. The approach is demonstrated through the use of a state-of-the-art monochromatic neutron diffractometer at the Institut Laue-Langevin (ILL) in combination with crystals of perdeuterated protein that minimise the level of hydrogen incoherent scattering and enhance the visibility of the anomalous signal. The protein used was rubredoxin in which cadmium replaced the iron at the iron-sulphur site. While this study was carried out using a steady-state neutron beam source, the results will be of major interest for capabilities at existing and emerging spallation neutron sources where time-of-flight instruments provide inherent energy discrimination. In particular this capability may be expected to offer unique opportunities to a rapidly developing structural biology community where there is increasing interest in the identification of protonation states, protein/water interactions and protein-ligand interactions – all of which are of central importance to a wide range of fundamental and applied areas in the biosciences.

CD4 is expressed on the surface of specific leukocytes where it plays a key role in the activation of immunostimulatory T-cells and acts as a primary receptor for HIV-1 entry. CD4 has four ecto-domains (D1-D4) of which D1, D2, and D4 contain disulfide bonds. Although disulfide bonds commonly serve structural or catalytic functions, a rare class of disulfide bonds possessing unusually high dihedral strain energy and a relative ease of reduction can impact protein function by shuffling their redox state. D2 of CD4 possesses one such "allosteric" disulfide. While it is becoming accepted that redox exchange of the D2 allosteric disulfide plays an essential role in regulating CD4 activity, the biophysical consequences of its reduction remain incompletely understood. By analyzing the hydrodynamic volume, secondary structure, and thermal stability of the reduced and nonreduced forms of the single D1 and D2 domains, as well as the various redox isomers of two domain CD4, we have shown that ablation of the allosteric disulfide bond in domain 2 results in both a favorable structural collapse and an increase in the stability of CD4. Conversely, ablating the structural disulfide of D1 results in destabilizing structural rearrangements in CD4. These findings expand our understanding of the mechanisms by which oxidoreduction of the D2 allosteric disulfide regulates CD4 function; they reveal the intrinsic disulfide-dependent metastability of D2 and illustrate that redox shuffling of the allosteric disulfide results in previously undescribed conformational changes in CD4 that are likely important for its interaction with its protein partners.